A case series evaluating the effect of esmolol therapy to treat hypoxemia in COVID-19 patients on VV-ECMO.

When COVID-19 ARDS abolishes pulmonary function, VV-ECMO can provide gas exchange. If oxygenation remains insufficient despite maximal VV-ECMO support, the addition of esmolol has been proposed. Conflict exists, however, as to the oxygenation level which should trigger beta-blocker initiation. We evaluated the effect of esmolol therapy on oxygenation and oxygen delivery in patients with negligible native lung function and various degrees of hypoxemia despite maximal VV-ECMO support. We found that, in COVID-19 patients with negligible pulmonary gas exchange, the generalized use of esmolol administration to raise arterial oxygenation by slowing heart rate and thereby match native cardiac output to maximal attainable VV ECMO flows actually reduces systemic oxygen delivery in many cases.

Renin-Angiotensin System Modulation With Synthetic Angiotensin (1-7) and Angiotensin II Type 1 Receptor-Biased Ligand in Adults With COVID-19: Two Randomized Clinical Trials.

Importance: Preclinical models suggest dysregulation of the renin-angiotensin system (RAS) caused by SARS-CoV-2 infection may increase the relative activity of angiotensin II compared with angiotensin (1-7) and may be an important contributor to COVID-19 pathophysiology. Objective: To evaluate the efficacy and safety of RAS modulation using 2 investigational RAS agents, TXA-127 (synthetic angiotensin [1-7]) and TRV-027 (an angiotensin II type 1 receptor-biased ligand), that are hypothesized to potentiate the action of angiotensin (1-7) and mitigate the action of the angiotensin II. Design, Setting, and Participants: Two randomized clinical trials including adults hospitalized with acute COVID-19 and new-onset hypoxemia were conducted at 35 sites in the US between July 22, 2021, and April 20, 2022; last follow-up visit: July 26, 2022. Interventions: A 0.5-mg/kg intravenous infusion of TXA-127 once daily for 5 days or placebo. A 12-mg/h continuous intravenous infusion of TRV-027 for 5 days or placebo. Main Outcomes and Measures: The primary outcome was oxygen-free days, an ordinal outcome that classifies a patient's status at day 28 based on mortality and duration of supplemental oxygen use; an adjusted odds ratio (OR) greater than 1.0 indicated superiority of the RAS agent vs placebo. A key secondary outcome was 28-day all-cause mortality. Safety outcomes included allergic reaction, new kidney replacement therapy, and hypotension. Results: Both trials met prespecified early stopping criteria for a low probability of efficacy. Of 343 patients in the TXA-127 trial (226 [65.9%] aged 31-64 years, 200 [58.3%] men, 225 [65.6%] White, and 274 [79.9%] not Hispanic), 170 received TXA-127 and 173 received placebo. Of 290 patients in the TRV-027 trial (199 [68.6%] aged 31-64 years, 168 [57.9%] men, 195 [67.2%] White, and 225 [77.6%] not Hispanic), 145 received TRV-027 and 145 received placebo. Compared with placebo, both TXA-127 (unadjusted mean difference, -2.3 [95% CrI, -4.8 to 0.2]; adjusted OR, 0.88 [95% CrI, 0.59 to 1.30]) and TRV-027 (unadjusted mean difference, -2.4 [95% CrI, -5.1 to 0.3]; adjusted OR, 0.74 [95% CrI, 0.48 to 1.13]) resulted in no difference in oxygen-free days. In the TXA-127 trial, 28-day all-cause mortality occurred in 22 of 163 patients (13.5%) in the TXA-127 group vs 22 of 166 patients (13.3%) in the placebo group (adjusted OR, 0.83 [95% CrI, 0.41 to 1.66]). In the TRV-027 trial, 28-day all-cause mortality occurred in 29 of 141 patients (20.6%) in the TRV-027 group vs 18 of 140 patients (12.9%) in the placebo group (adjusted OR, 1.52 [95% CrI, 0.75 to 3.08]). The frequency of the safety outcomes was similar with either TXA-127 or TRV-027 vs placebo. Conclusions and Relevance: In adults with severe COVID-19, RAS modulation (TXA-127 or TRV-027) did not improve oxygen-free days vs placebo. These results do not support the hypotheses that pharmacological interventions that selectively block the angiotensin II type 1 receptor or increase angiotensin (1-7) improve outcomes for patients with severe COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04924660.

Nitric oxide mediated hypoxia dynamics in COVID-19.

Several COVID-19 patients frequently experience with happy hypoxia. Sometimes, the level of nitric oxide (NO) in COVID-19 patients was found to be greater than in non-COVID-19 hypoxemics and most of the cases lower. Induced or inhaled NO has a long history of usage as a therapy for hypoxemia. Excessive production of ROS and oxidative stress lower the NO level and stimulates mitochondrial malfunction is the primary cause of hypoxia-mediated mortality in COVID-19. Higher level of NO in mitochondria also the cause of dysfunction, because, excess NO can also diffuse quickly into mitochondria or through mitochondrial nitric oxide synthase (NOS). A precise dose of NO may increase oxygenation while also acting as an effective inhibitor of cytokine storm. NOS inhibitors may be used in conjunction with iNO therapy to compensate for the patient's optimal NO level. NO play a key role in COVID-19 happy hypoxia and a crucial component in the COVID-19 pathogenesis that demands a reliable and easily accessible biomarker to monitor.

Metabolic dysfunction associated fatty liver disease and coronavirus disease 2019: clinical relationship and current management.

The coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). At present, the COVID-19 has been prevalent worldwide for more than a year and caused more than four million deaths. Liver injury was frequently observed in patients with COVID-19. Recently, a new definition of metabolic dysfunction associated fatty liver disease (MAFLD) was proposed by a panel of international experts, and the relationship between MAFLD and COVID-19 has been actively investigated. Several previous studies indicated that the patients with MAFLD had a higher prevalence of COVID-19 and a tendency to develop severe type of respiratory infection, and others indicated that liver injury would be exacerbated in the patients with MAFLD once infected with COVID-19. The mechanism underlying the relationship between MAFLD and COVID-19 infection has not been thoroughly investigated, and recent studies indicated that multifactorial mechanisms, such as altered host angiotensin converting enzyme 2 (ACE2) receptor expression, direct viral attack, disruption of cholangiocyte function, systemic inflammatory reaction, drug-induced liver injury, hepatic ischemic and hypoxic injury, and MAFLD-related glucose and lipid metabolic disorders, might jointly contribute to both of the adverse hepatic and respiratory outcomes. In this review, we discussed the relationship between MAFLD and COVID-19 based on current available literature, and summarized the recommendations for clinical management of MAFLD patients during the pandemic of COVID-19.

Severe Post-COVID-19 Organizing Pneumonia during Cancer Immunochemotherapy.

A 44-year-old man developed coronavirus disease 2019 (COVID-19) pneumonia during immunochemotherapy consisting of carboplatin, paclitaxel, and pembrolizumab for non-small cell lung cancer. Low-grade fever, followed by mild hypoxemia, and febrile neutropenia, were observed, and granulocyte colony-stimulating factor (G-CSF) was administered until the recovery of neutropenia, when he developed a high fever, severe hypoxemia, and hypotension accompanied by consolidation in the bilateral lungs. His conditions promptly improved after treatment including hydrocortisone and the primary and metastatic tumors remained regressed for 10 months without further treatment. Post-COVID-19 organizing pneumonia during cancer immunochemotherapy can be aggravated by immune-checkpoint inhibitors and G-CSF.

Inhaled Nitric Oxide for Clinical Management of COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: Severe COVID-19 is associated with hypoxemia and acute respiratory distress syndrome (ARDS), which may predispose multiorgan failure and death. Inhaled nitric oxide (iNO) is a clinical vasodilator used in the management of acute respiratory distress syndrome (ARDS). This study evaluated the response rate to iNO in patients with COVID-19-ARDS. METHOD: We searched Medline and Embase databases in May 2022, and data on the use of iNO in the treatment of ARDS in COVID-19 patients were synthesized from studies that satisfied predefined inclusion criteria. A systematic synthesis of data was performed followed by meta-analysis. We performed the funnel plot and leave-one-out sensitivity test on the included studies to assess publication bias and possible exaggerated effect size. We compared the effect size of the studies from the Unites States with those from other countries and performed meta-regression to assess the effect of age, year of publication, and concomitant vasodilator use on the effect size. RESULTS: A total of 17 studies (including 712 COVID-19 patients) were included in this systematic review of which 8 studies (involving 265 COVID-19 patients) were subjected to meta-analysis. The overall response rate was 66% (95% CI, 47-84%) with significantly high between-studies heterogeneity (I2 = 94%, p < 0.001). The funnel plot showed publication bias, although the sensitivity test using leave-one-out analysis showed that removing any of the study does not remove the significance of the result. The response rate was higher in the Unites States, and meta-regression showed that age, year of publication, and use of concomitant vasodilators did not influence the response rate to iNO. CONCLUSION: iNO therapy is valuable in the treatment of hypoxemia in COVID-19 patients and may improve systemic oxygenation in patients with COVID-19-ARDS. Future studies should investigate the mechanism of the activity of iNO in COVID-19 patients to provide insight into the unexplored potential of iNO in general ARDS.

Desidustat: First Approval.

Desidustat (Oxemia™) is an orally bioavailable, small molecule, hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitor developed by Zydus Cadila for the treatment of anaemia associated with chronic kidney disease (CKD), COVID-2019 infections and chemotherapy induced anaemia. Desidustat inhibits prolyl hydroxylase domain enzymes, resulting in the stabilisation of hypoxia-inducible factor which stimulates erythropoietin production and erythropoiesis. In March 2022, desidustat received its first approval in India for the treatment of anaemia in adults with CKD who are either on dialysis or not on dialysis. Desidustat is in clinical development in China for the treatment of anaemia in patients with CKD, in Mexico for the management of COVID-2019 infections and in the USA for the treatment of chemotherapy induced anaemia. This article summarizes the milestones in the development of desidustat leading to this first approval for anaemia associated with CKD.

Inhaled nitric oxide as temporary respiratory stabilization in patients with COVID-19 related respiratory failure (INOCOV): Study protocol for a randomized controlled trial.

BACKGROUND: In March 2020, WHO announced the COVID-19 a pandemic and a major global public health emergency. Mortality from COVID-19 is rapidly increasing globally, with acute respiratory failure as the predominant cause of death. Many patients experience severe hypoxia and life-threatening respiratory failure often requiring mechanical ventilation. To increase safety margins during emergency anaesthesia and rapid sequence intubation (RSI), patients are preoxygenated with a closed facemask with high-flow oxygen and positive end-expiratory pressure (PEEP). Due to the high shunt fraction of deoxygenated blood through the lungs frequently described in COVID-19 however, these measures may be insufficient to avoid harmful hypoxemia. Preoxygenation with inhaled nitric oxide (iNO) potentially reduces the shunt fraction and may thus allow for the necessary margins of safety during RSI. METHODS AND DESIGN: The INOCOV protocol describes a phase II pharmacological trial of inhaled nitric oxide (iNO) as an adjunct to standard of care with medical oxygen in initial airway and ventilation management of patients with known or suspected COVID-19 in acute respiratory failure. The trial is parallel two-arm, randomized, controlled, blinded trial. The primary outcome measure is the change in oxygen saturation (SpO2), and the null hypothesis is that there is no difference in the change in SpO2 following initiation of iNO. TRIAL REGISTRATION: EudraCT number 2020-001656-18; WHO UTN: U1111-1250-1698. Protocol version: 2.0 (June 25th, 2021).

COVID-19 coagulopathy - what should we treat?

NEW FINDINGS: What is the topic of this review? Overview of the coagulation abnormalities, including elevated D-dimers widely reported with COVID-19, often labelled as COVID coagulopathy. What advances does it highlight? The review highlights the changes in bronchoalveolar haemostasis due to apoptosis of alveolar cells, which contributes to acute lung injury and acute respiratory distress syndrome; the pathophysiological mechanisms, including endothelial dysfunction and damage responsible for thrombosis of pulmonary microcirculation and potential contribution to the hypoxaemia of COVID-19 acute lung injury; and changes in coagulation proteins responsible for the hypercoagulability and increased risk of thrombosis in other venous and arterial beds. The rationale for anticoagulation and fibrinolytic therapies is detailed, and potential confounders that might have led to less than expected improvement in the various randomised controlled trials are considered. ABSTRACT: Coronavirus disease 19 (COVID-19) causes acute lung injury with diffuse alveolar damage, alveolar-capillary barrier disruption, thrombin generation and alveolar fibrin deposition. Clinically, hypoxaemia is associated with preserved lung compliance early in the disease, suggesting the lack of excessive fluid accumulation typical of other lung injuries. Notably, autopsy studies demonstrate infection of the endothelium with extensive capillary thrombosis distinct from the embolic thrombi in pulmonary arteries. The inflammatory thrombosis in pulmonary vasculature secondary to endothelial infection and dysfunction appears to contribute to hypoxaemia. This is associated with elevated D-dimers and acquired hypercoagulability with an increased risk of deep vein thrombosis. Hypercoagulability is secondary to elevated plasma tissue factor levels, von Willebrand factor, fibrinogen, reduced ADAMTS-13 with platelet activation and inhibition of fibrinolysis. Multi-platform randomised controlled studies of systemic therapeutic anticoagulation with unfractionated and low molecular mass heparins demonstrated a survival benefit over standard care with full-dose anticoagulation in patients with non-severe disease who require supplemental oxygen, but not in severe disease requiring ventilatory support. Late intervention and the heterogeneous nature of enrolled patients can potentially explain the apparent lack of benefit in severe disease. Improvement in oxygenation has been demonstrated with intravenous fibrinolytics in small studies. Inhaled anticoagulants, thrombolytic agents and non-specific proteolytic drugs in clinical trials for decreasing alveolar fibrin deposition might benefit early disease. Essentially, COVID-19 is a multi-system disorder with pulmonary vascular inflammatory thrombosis that requires an interdisciplinary approach to combination therapies addressing both inflammation and intravascular thrombosis or alveolar fibrin deposits to improve outcomes.

Nitric oxide versus epoprostenol for refractory hypoxemia in Covid-19.

OBJECTIVE: To compare the efficacy and outcomes with inhaled nitric oxide (iNO) and inhaled epoprostenol (iEPO) in patients with refractory hypoxemia due to COVID-19. DESIGN: Retrospective Cohort Study. SETTING: Single health system multicenter academic teaching hospitals. PATIENTS OR SUBJECTS: Age group of 18-80 years admitted to the medical ICU. INTERVENTIONS: Mechanically ventilated patients with COVID-19 infection, who received either iNO or iEPO between March 1st, 2020, and June 30th, 2020. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the change in the PaO2/FiO2 (P/F) ratio 1 hour after initiation of pulmonary vasodilator therapy. Secondary outcomes include P/F ratios on days 1-3 after initiation, positive response in P/F ratio (increase of at least 20% in PaO2), total days of treatment, rebound hypoxemia (if there was a drop in oxygen saturation after treatment was stopped), ventilator free days (if any patient was extubated), days in ICU, days to extubation, days to tracheostomy, mortality days after intubation, 30-day survival and mortality. 183 patients were excluded, as they received both iNO and iEPO. Of the remaining 103 patients, 62 received iEPO and 41 received iNO. The severity of ARDS was similar in both groups. Change in P/F ratio at one hour was 116 (70.3) with iNO and 107 (57.6) with iEPO (Mean/SD). Twenty-two (53.7%) patients in the iNO group and 25 (40.3%) in the iEPO group were responders to pulmonary vasodilators n(%)(p = 0.152) (more than 20% increase in partial pressure of oxygen, Pao2), and 18 (43.9%) and 31 (50%) patients in the iNO and iEPO group (p = 0.685), respectively, had rebound hypoxemia. Only 7 patients in the cohort achieved ventilator free days (3 in the iEPO group and 4 in iNO group). CONCLUSIONS: We found no significant difference between iNO and iEPO in terms of change in P/F ratio, duration of mechanical ventilation, ICU, in-hospital mortality in this cohort of mechanically ventilated patients with COVID-19. Larger, prospective studies are necessary to validate these results.

Multisystem inflammatory syndrome in an adult with severe hypoxaemia and thyroiditis responsive to corticosteroid and interleukin 6 inhibitor treatment.

Multisystem inflammatory syndrome in adults (MIS-A) has been reported as a rare but severe consequence of COVID-19 infection. Adult patients were more likely to present with hypotension and cardiac illness when compared with multisystem inflammatory syndrome in children. Although the exact prevalence of MIS-A is unknown, more cases have been observed in men and younger adults. The pathophysiology of MIS-A is also unclear, but is thought to be caused by a delayed, dysregulated immune response. Given no established guideline for treatment of MIS-A, treatment has been based on case reports. We present a case of MIS-A in a woman in her 60s who had severe hypotension, progressive dyspnoea, massive pleural effusion, hypoxaemia, thyroiditis and multiple organ failure, which dramatically improved after treatment with corticosteroid and interleukin 6 inhibitor.

Compassionate use of Pulmonary Vasodilators in Acute Severe Hypoxic Respiratory Failure due to COVID-19.

BACKGROUND: There have been over 200 million cases and 4.4 million deaths from COVID-19 worldwide. Despite the lack of robust evidence one potential treatment for COVID-19 associated severe hypoxaemia is inhaled pulmonary vasodilator (IPVD) therapy, using either nitric oxide (iNO) or prostaglandins. We describe the implementation of, and outcomes from, a protocol using IPVDs in a cohort of patients with severe COVID-19 associated respiratory failure receiving maximal conventional support. METHODS: Prospectively collected data from adult patients with SARS-CoV-2 admitted to the intensive care unit (ICU) at a large teaching hospital were analysed for the period 14th March 2020 - 11th February 2021. An IPVD was considered if the PaO2/FiO2 (PF) ratio was less than 13.3kPa despite maximal conventional therapy. Nitric oxide was commenced at 20ppm and titrated to response. If oxygenation improved Iloprost nebulisers were commenced and iNO weaned. The primary outcome was percentage changes in PF ratio and Alveolar-arterial (A-a) gradient. RESULTS: Fifty-nine patients received IPVD therapy during the study period. The median PF ratio before IPVD therapy was commenced was 11.33kPa (9.93-12.91). Patients receiving an IPVD had a lower PF ratio (14.37 vs. 16.37kPa, p = 0.002) and higher APACHE-II score (17 vs. 13, p = 0.028) at ICU admission. At 72 hours after initiating an IPVD the median improvement in PF ratio was 33.9% (-4.3-84.1). At 72 hours changes in PF ratio (70.8 vs. -4.1%, p < 0.001) and reduction in A-a gradient (44.7 vs. 14.8%, p < 0.001) differed significantly between survivors (n = 33) and non-survivors (n = 26). CONCLUSIONS: The response to IPVDs in patients with COVID-19 associated acute hypoxic respiratory failure differed significantly between survivors and non-survivors. Both iNO and prostaglandins may offer therapeutic options for patients with severe refractory hypoxaemia due to COVID-19. The use of inhaled prostaglandins, and iNO where feasible, should be studied in adequately powered prospective randomised trials.

Nitric Oxide Inhalation Therapy Attenuates Postoperative Hypoxemia in Obese Patients with Acute Type A Aortic Dissection.

Objective: To investigate the differences between inhaled nitric oxide (iNO) treatment and conventional therapy in the treatment of postoperative hypoxemia in obese patients with acute type A aortic dissection (ATAAD). Methods: ATAAD patients diagnosed and treated with emergency surgery in our hospital from June 2017 to December 2019 were retrospectively analyzed. Patients with postoperative hypoxemia were divided into the iNO group and control group. Propensity score matching was used to analyze clinical characteristics and results of the two groups. Results: A total of 218 ATAAD patients with BMI ≥ 25 were treated with surgery. Among them, 115 patients developed refractory hypoxemia (64 in the control group and 51 in the iNO group). Patients in the iNO group had significantly shorter invasive mechanical ventilation time, intensive care unit (ICU) stay, and hospital stay. After 6 h of iNO treatment, the PaO2/FiO2 ratio in the iNO group increased significantly, and this ratio was higher than that in the control group at 6, 12, 24, 48, and 72 h after treatment. Conclusion: Low-dose iNO could improve oxygenation and shorten mechanical ventilation and ICU stay in patients with hypoxemia after ATAAD surgery, but without significant side effects or increase in postoperative mortality or morbidity. These findings provide a basis for a randomized multicenter controlled trial to assess the efficacy of iNO in the treatment of hypoxemia after ATAAD surgery.

Critical role of nitric oxide in impeding COVID-19 transmission and prevention: a promising possibility.

COVID-19 is a serious respiratory infection caused by a beta-coronavirus that is closely linked to SARS. Hypoxemia is a symptom of infection, which is accompanied by acute respiratory distress syndrome (ARDS). Augmenting supplementary oxygen may not always improve oxygen saturation; reversing hypoxemia in COVID-19 necessitates sophisticated means to promote oxygen transfer from alveoli to blood. Inhaled nitric oxide (iNO) has been shown to inhibit the multiplication of the respiratory coronavirus, a property that distinguishes it from other vasodilators. These findings imply that NO may have a crucial role in the therapy of COVID-19, indicating research into optimal methods to restore pulmonary physiology. According to clinical and experimental data, NO is a selective vasodilator proven to restore oxygenation by helping to normalize shunts and ventilation/perfusion mismatches. This study examines the role of NO in COVID-19 in terms of its specific physiological and biochemical properties, as well as the possibility of using inhaled NO as a standard therapy. We have also discussed how NO could be used to prevent and cure COVID-19, in addition to the limitations of NO.

Evaluation of aerosolized epoprostenol for hypoxemia in non-intubated patients with coronavirus disease 2019.

OBJECTIVES: Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) frequently present with a febrile illness that may progress to pneumonia and hypoxic respiratory failure. Aerosolized epoprostenol (aEPO) has been evaluated in patients with acute respiratory distress syndrome and refractory hypoxemia. A paucity of literature has assessed the impact of aEPO in patients with SARS-CoV-2 receiving oxygen support with high flow nasal cannula (HFNC). The objective of this study was to evaluate whether aEPO added to HFNC prevents intubation and/or prolong time to intubation compared to controls only treated with HFNC, guided by oxygen saturation goals. METHODS: This was a single-center, retrospective study of adult patients infected with coronavirus 2019 (COVID-19) and admitted to the medical intensive care unit. A total of 60 patients were included. Thirty patients were included in the treatment, and 30 in the control group, respectively. Among patients included in the treatment group, response to therapy was assessed. The need for mechanical ventilation and hospital mortality between responders vs. non-responders was evaluated. RESULTS: The primary outcome of mechanical ventilation was not statistically different between groups. Time from HFNC initiation to intubation was significantly prolonged in the treatment group compared to the control group (5.7 days vs. 2.3 days, P = 0.001). There was no statistically significant difference between groups in mortality or length of stay. Patients deemed responders to aEPO had a lower rate of mechanical ventilation (50% vs 88%, P = 0.025) and mortality (21% vs 63%, P = 0.024), compared with non-responders. CONCLUSION: The utilization of aEPO in COVID-19 patients treated with HFNC is not associated with a reduction in the rate of mechanical ventilation. Nevertheless, the application of this strategy may prolong the time to invasive mechanical ventilation, without affecting other clinical outcomes.

Effectiveness of ivermectin-based multidrug therapy in severely hypoxic, ambulatory COVID-19 patients.

Aims: Ivermectin is a safe, inexpensive and effective early COVID-19 treatment validated in 20+ random, controlled trials. Having developed combination therapies for Helicobacter pylori, the authors present a highly effective COVID-19 therapeutic combination, stemming from clinical observations. Patients & methods: In 24 COVID-19 subjects refusing hospitalization with high-risk features, hypoxia and untreated moderate to severe symptoms averaging 9 days, the authors administered this novel combination of ivermectin, doxycycline, zinc and vitamins D and C. Results & conclusions: All subjects resolved symptoms (in 11 days on average), and oxygen saturation improved in 24 h (87.4% to 93.1%; p = 0.001). There were no hospitalizations or deaths, less than (p < 0.002 or 0.05, respectively) background-matched CDC database controls. Triple combination therapy is safe and effective even when used in outpatients with moderate to severe symptoms. Clinical Trial Registration: NCT04482686 (ClinicalTrial.gov).

Nanocurcumin formulation: a possible therapeutic agent for post COVID inflammatory syndrome.

Over the last twenty months, the attention of the world has been focusing on managing the unprecedented and devastating wave of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) and mitigating its impacts. Recent findings indicated that high levels of pro-inflammatory cytokines are leading cause of poor prognosis in severely ill COVID-19 patients. Presently, the multiple variants and highly contagious nature of virus makes challenge humongous. The shortage and vaccine hesitancy also prompted to develop antiviral therapeutic agents to manage this pandemic. Nanocurcumin has potential antiviral activities and also beneficial in post COVID inflammatory complications. We have developed nanocurcumin based formulation using pyrroloquinoline quinone (PQQ) which protects cardio-pulmonary function and mitochondrial homeostasis in hypobaric hypoxia induced right ventricular hypertrophy in animal model and human ventricular cardiomyocytes. Nanocurcumin based formulation (NCF) with improved bioavailability, has proven several holistic therapeutic effects including myocardial protection, and prevents edema formation, anti-inflammatory and antioxidant properties, maintaining metabolic and mitochondrial homeostasis under hypoxic condition. The post COVID-inflammatory syndrome also reported to cause impaired heart function, lung injuries and increased C-reactive protein level in severely ill patients. Thus, we speculate that NCF could be a new treatment option to manage post COVID-19 inflammatory syndrome.

Role of systemic corticosteroids in preventing hypoxia among patients with mild COVID-19: An observational study.

Use of systemic corticosteroids is well-established in COVID-19 patients with hypoxia; however, there is scant data on its role in patients with mild disease and prolonged symptoms as a measure to prevent disease progression. The aim of this study is to evaluate the role of systemic corticosteroids in preventing hypoxia (SpO2 ≤ 93% on room-air) among mild COVID-19 patients. An observational study was conducted among symptomatic COVID-19 patients taking oral corticosteroids and attending institute teleconsultation facility between 10th-30th June 2021. Patients who were already on corticosteroids for other indication or required oxygen supplementation before or within 24-hours of initiation of corticosteroids were excluded. A total of 140 consecutive symptomatic COVID-19 patients were included. Higher baseline C-reactive protein (OR: 1.03, 95% CI: 1.02-1.06, p < 0.001) and early systemic corticosteroid (within 7 days) initiation (OR: 6.5, 95% CI: 2.1-20.1, p = 0.001) were independent risk factors for developing hypoxia (SpO2 ≤ 93%). Progression to hypoxia was significantly higher in patients who received corticosteroids before day 7 of illness (36.7%, 95% CI, 23.4-51.7%) compared to ≥ 7 of illness (14.3%, 95% CI, 7.8-23.2%) for persistent fever. Systemic corticosteroids within 7 days from symptom-onset were harmful and increased the risk of progression to hypoxia, whereas it may decrease the risk of progression when administered on or beyond 7 days in patients with mild COVID-19 and persistent symptoms. A well-designed randomised controlled trial is required to validate the findings.

Post-COVID-19 interstitial lung disease presenting with profound hypoxemia: Report of three cases demonstrating a good response to high-dose corticosteroid therapy.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which leads to critical pneumonia, although the clinical courses vary. In some cases, COVID-19 pneumonia causes secondary pulmonary fibrosis, which can retain radiological changes and prolong respiratory symptoms. Interstitial lung disease (ILD) secondary to COVID-19 is thought to be caused by multiple pathologies, such as excessive cytokines and abnormal repair processes elaborated by lung cells (epithelium, mesenchyme, and alveolar macrophages) after lung injury rather than viral invasion itself. Immunosuppression therapy may improve chronic respiratory symptoms and radiological changes in post-COVID-19 ILD, although the treatment is not yet established. Herein, we report three patients with post-COVID-19 ILD who presented with profound hypoxemia that had a good response to high-dose corticosteroid therapy. Further and larger studies are needed to establish post-COVID-19 ILD.